Single cell refractive index measurement via lab-on-a-chip system

• Main Author: Chin, Lip Ket
• Other Authors: Liu Aiqun
• Format: Theses and Dissertations
• Language: English
• Published: 2011
• Subjects: DRNTU::Engineering::Electrical and electronic engineering::Optics, optoelectronics, photonics
• Online Access: https://hdl.handle.net/10356/44847
• Institution: Nanyang Technological University

This doctorate thesis focuses on the design, fabrication and experiments of single living cell refractometers using Lab-on-a-chip (LOC) technology. Through the Lab-on-a-Chip technology, various on-chip cell refractometric systems are designed to address the objectives of macro to micro optical system integration; fully integrated microfluidic and cell manipulating functionalities; compact, biocompatible and highly portable device. Specifically, three LOC devices have been designed and investigated: the on-chip grating interferometer, the optofluidic Fabry-Pérot refractometer, and the complementary microfluidic Fabry-Pérot resonant system. In the development of the on-chip grating interferometer based on the fiber Bragg gratings, the various aspects of grating interferometer are studied and modeled. A theoretical study of the frequency response for the variation of the optical path length in the cavity is carried out, and a simplified model based on Fabry-Pérot (FP) resonant cavity is established. The differential measurement scheme is employed for the simultaneous measurement of the cell refractive index and size. Then, a fiber-based optical trapping mechanism is used for single cell trapping in the cavity. Besides, the microfluidic network is designed to facilitate single cell measurement and realize the differential measurement scheme. Hydrodynamic focusing mechanism is designed for single cell alignment, and then multiphase plug generating mechanism for single cell encapsulation. In the cavity, plug mixing mechanism is designed to change the extracellular environment. The on-chip grating interferometer is finally fabricated and packaged with interconnections for external equipment. The measurement of Madin-Darby canine kidney (MDCK) cell using the fabricated LOC device is presented with a precision of 0.001 refractive index unit (RIU). The development of optofluidic FP refractometer begins with the study of the essential criteria for high-finesse resonant cavity. Based on the theoretical study, a novel design of LOC FP refractometer with the integration of a pair of liquid microlenses is presented. The liquid microlens is simulated to optimize the lens formation process and to match the perfect lens profile. The liquid microlenses provide real-time tenability to optimize the finesse of the resonant cavity. Based on the design, the optofluidic FP refractometer is fabricated, packaged and experimented. As compared to the previous LOC device, the fabrication process is relatively simpler which does not require complicated fabrication process such as the Bragg grating writing system. The finesse of the FP resonant cavity is improved by 5 folds to 18.79. The measurement of MDCK cell is presented and a precision of 0.0008 RIU is achieved.